Conventionally, separation technologies including liquid chromatography, supercritical chromatography and gas chromatography as a method of isolating a desired component from an isomer mixture containing two or more components have widely been used for various kinds of analyses such as environmental analysis, metabolic analysis and impurity analysis. These separation technologies are considered to be a kind of analysis technology, and have an aspect different from a technology for isolating a particular component with a high purity from a mixture that includes plural components. In other words, the concept of “separation” in the field of analysis technology means separating each component from a mixture that includes plural components with such a purity as to be required to identify each component. Consequently contamination of a component with other components unavoidably accompanies “separation” in this sense. On the other hand, in the fields of separation of physiologically active substances and separation of optically active antipodes, “separation” means the separation of a single substance at a high purity. Therefore the separation of, for example, optically active compounds at a high purity cannot be achieved by separation technologies used for ordinary chemical analyses. Recently, researchers began to employ simulated moving bed chromatographic separation methods to achieve separation on an industrial scale at a high purity.
Under these circumstances demand for fillers to be used for separating optical isomers has been increasing, and technologies to produce fillers having stable qualities on a large scale have been desired.
One of the known methods of producing a filler for separating optical isomers is a method in which silica gel is immersed in a solution of polysaccharide derivatives and the solvent is distilled off from the solution, proposed by Okamoto et al. (Y. Okamoto, M. Kawashima and K. Hatada, J. Am. Chem. 106, 5357, 1984). The others are an impact method in high speed flow described in JP 3-2009, B and a method of preparing a carrier by spraying disclosed in JP 63-84626, A.
These methods can successfully produce a filler for separating optical isomers in an amount of some hundred grams, an amount typically used on a laboratory scale. The produced filler has a separation ability that is satisfactory to some extent.
However, when a researcher tried to produce a filler for separating optical isomers on a greater scale, in an amount of 1 kg to several ten kg, it turned out that a filler with an excellent separation ability could not always be obtained by this method. For example, to make the carrier uniformly support active components such as polysaccharide derivatives and to sprinkle the inner walls of pores of the carrier with the polysaccharide derivatives are difficult. Besides, after the completion of the supporting process, the solvent remaining in the carrier is uneven. Further, granules are formed through agglomeration of unsupported polysaccharide derivatives. These factors lower the separation ability to such an extent that the obtained filler cannot practically be used.
Also, when the columns are filled with a filler for separating optical isomers and optical isomers are separated, it is preferable that the columns should have a smaller pressure loss to let liquid, gas or supercritical fluid pass through. In view of this requirement, generally, methods that might break the carrier cannot be employed. Therefore, although the above mentioned methods may provide excellent fillers in a laboratory scale production, the methods cannot always provide good fillers in a larger scale, e.g. a commercial scale production due to a larger mixing power applied to the carrier and the polysaccharide derivatives, or change in other conditions.
An objective of the present invention is to provide a process of producing, on a commercial scale, a filler for separating optical isomers that has an excellent separation ability, a filler for separating optical isomers having an excellent separation ability that is produced on a commercial scale, and a method of using the filler.
Another objective of the present invention is to provide a process of producing a filler for separating optical isomers, which filler comprises a carrier and an optically active polymer compound supported on the carrier, the filler thus produced, and a method of using the filler.